Regulation Of Deubiquitinase USP21 On FOXP3?GATA3 Expression In CD4+CD25+ T Cells In Allergic Airway Inflammation

Allergic airway inflammation is a Th2-geared immune disease.Regulatory T cells(Tregs)can regulate the effector function of Th2 cells.FOXP3 is essential for the differentiation and function of Tregs.And GATA3 not only affects the polarization and function of Th2,but also plays an important role in Tregs.During inflammation,GATA3 can maintain the accumulation of Tregs to the inflammatory site and the high levels of FOXP3 in Treg cells.The depletion of GATA3 in Tregs leads to an inflammatory disorder in mice.USP21 is a member of the ubiquitin specific protease(USP)family of deubiquitinating enzymes(DUBs).In our previous study,we have already found that GATA3 is one of the substrate of USP21 which prevents the degradation of GATA3,and upon T-cell receptor(TCR)stimulation FOXP3 can directly bind to the USP21 gene promoter to activate its transcription.So in Tregs,USP21,GATA3,and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg cell activity.This study focuses on the Regulation of deubiquitinase USP21 on the expression of FOXP3,GATA3 in regulatory T cells in allergic airway inflammation.C57BL/6 mice were sensitized to ovalbumin(OVA)by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA.The concentrations of total IgE in the serum and the Th2 cytokine IL-4?IL-5 and IL-13 in lung tissue were measured by ELISA.The extents of inflammatory cells infiltration were evaluated on the lung histology of eosin-stained(HE)staining.The results are consistent.The inflammation in the experimental group is significantly more serious than the control group.We have already verified that USP21 can prevent the degradation of GATA3 through reversing its ubiquitination.Furthermore,in Treg cells,USP21,GATA3,and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg cell activity.Next,we did the immunohistochemistry and western blot to check USP21 expression in the lung,the results indicate that up OVA stimulation the expression level of USP21 is higher in the OVA group.Also the flowcytometry analysis indicates in the lung tissue and the peripheral blood,the expression level of USP21 in Treg is higher in the OVA group.To figure out the changes in the expression of FOXP3 and GATA3 in Tregs,we do the flow cytometry analysis.In the lung tissue and peripheral blood,the expression level of FOXP3 is higher in the OVA group compared to the control group.Although the expression level of GATA3 in the peripheral blood in Treg is similar between two groups,in the lung tissue its expression increased significantly in the OVA group.And we find that the number of Treg in the lung tissue and peripheral blood significantly decreased in the OVA group compared to the control group.Conclusion: In allergic airway inflammation,the expression of USP21 in Treg increased in the lung tissue and the peripheral blood,and it can up-regulate the expression of FOXP3 and GATA3 in Tregs.